Sensitivity of CYP1A1 mRNA inducibility by dioxin is the same in Cyp1a2(+/+) wild-type and Cyp1a2(-/-) null mutant mice.
In mammals, the induction of experimental porphyria by halogenated aromatic hydrocarbons (HAHs) seems to be influenced by the levels of hepatic CYP1A2. The pharmacokinetics and relative rates of uptake and storage of HAHs in the liver are correlated with hepatic CYP1A2 concentrations. It is possible that these rates of HAH uptake and storage might affect the expression of other HAH-inducible genes. The differential inducibility of liver CYP1A1 mRNA by dioxin was therefore compared in Cyp1a2(+/+) wild-type mice, Cyp1a2(+/-) heterozygotes, and Cyp1a2(-/-) homozygous null mutants. Using doses of dioxin over eight orders of magnitude (from 10[-12] to 10[-4] g/kg), we could detect no differences in the sensitivity of CYP1A1 mRNA inducibility. These data indicate that the complete absence of the microsomal CYP1A2 enzyme has no measurable effect on hepatic expression of the Cyp1a1, gene, the only other known member of the mammalian CYP1A cytochrome P450 subfamily.
Liang
H C
HC
Center for Environmental Genetics and Department of Environmental Health, University of Cincinnati Medical Center, OH 45267-0056, USA.
McKinnon
R A
RA
Nebert
D W
DW
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000502:physiology*; D004790:Enzyme Induction / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis*
D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2